Detection of inducible nitric oxide synthase (iNOS) mRNA by RT-PCR in ATL patients and HTLV-I infected cell lines: clinical features and apoptosis by NOS inhibitor.

Various tumors have been reported to express an inducible form of nitric oxide synthase (iNOS), and nitric oxide (NO) may affect the clinicopathological features of these tumors. Previously, Burkitt's lymphoma and Epstein-Barr virus (EBV)-infected cells were shown to express iNOS constitutively at a low level. We analyzed iNOS expression by the reverse transcriptase-polymerase reaction method (RT-PCR) in eight HTLV-I-infected cell lines (five were ATL-derived lines and there were in vitro transformed lines), nine ATL patients (three were chronic, two were acute, and four were lymphoma type), and an HTLV-I-negative T cell line (CEM). In four ATL derived and in all three in vitro transformed cell lines, iNOS was expressed constitutively, but it was not expressed in CEM cells. Four out of nine ATL patients also showed iNOS expression. The expression of iNOS was found in all subtypes of ATL. Three of four iNOS-positive patients had infiltration of ATL cells to organs such as skin, lung, or liver. In NOS inhibitor (NG-monomethyl-L-arginine: L-NMMA)-containing medium, an iNOS-positive ATL cell line (K3T) showed growth inhibition and DNA ladder. Although only a limited number of patients was analyzed, our results suggest that NO may be involved in the invasive character of ATL cells. The NOS inhibitor can induce apoptosis in an ATL cell line, as it does in EBV-infected cell lines.